Recent progress in prion biology Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative diseases of humans and animals. The underlying infectious agent, the prion, accumulates not only in the central nervous system (CNS) but also in secondary lymphoid organs. The role of the immune system in peripheral prion pathogenesis, while focusing on the mechanisms by which extraneural and extralymphatic prion infectivity develops will be discussed. Interestingly, the same pro-inflammatory cytokines and homeostatic chemokines that are involved in lymphoid neogenesis and compartmentalisation of immune cells appear to represent the crucial molecular switches responsible for the establishment of extraneural prion reservoirs.Professor Adriano Aguzzi, Institute of Neuropathology, University Hospital of Zürich, Switzerland 09.35 Removal and concentration of TSE infectivity from blood by use of PRDT affinity ligands incorporated into a filter device by Macopharma Using a high throughput selection method, Pathogen Removal and Diagnostics Technologies, PRDT, has obtained high affinity ligands that strongly bind both the abnormal form of the prion protein and TSE infectivity from both brain and blood. Impregnated into filters these resins have been incorporated by Macopharma into a stand alone device for removing TSE infectivity from red blood cells.Dr Robert Rohwer, Director of Molecular Neurovirology Unit,University of Maryland, Baltimore, USA 10.05 Critical factors influencing prion clearance and decontamination The unique biochemical properties of prions pose both challenges and opportunities for its clearance and decontamination. During therapeutic protein purification, prion particles can be removed by exploring their similarities with impurities. During equipment sanitisation, prion particles can be inactivated by unfolding of their native protein structure. Examples will be provided in support of both scenarios and discussed in the context of new information on blood infectivity.Dr Kang Cai, Virology/TSE, Research and Development, Talecris Biotherapeutics, USA 10.35 Morning coffee and poster / exhibition viewing time 11.00 TSE agent properties affecting TSE inactivation TSE strains are inactivated at different temperatures, dependent on strain of TSE agent but are also affected to a lesser extent by the phenotype of the PrP protein of the host animal. Greater thermostability can be induced by protein dehydration or fixation, leading to increased problems with TSE inactivation. Hence the mechanisms of TSE inactivation and their practical limits are being defined. These and other findings also suggest that diversity in the chemical structure of the TSE agent is required, which is covalently encoded and independent of the host.Dr Robert A. Somerville, Neuropathogenesis Unit, Institute for Animal Health, UK 11.30 Preparation of soluble infectious samples from scrapie- infected brain: A new tool to study the clearance of TSE agents during plasma fractionation This study describes a simple and fast protocol to prepare infectious material from scrapie- infected brains that is not contaminated with PrPTSE aggregates. This fraction is likely the most relevant material for endogenous spiking of human blood in validation experiments aimed at demonstrating procedures to remove or inactivate TSE infectious agents.Professor Maurizio Pocchiari, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Italy 12.00 Technology TutorialTechnology providers will host interactive educational tutorials which address the benefits of their technology in the filed of TSE’s. If you would like to host a tutorial, please contact: lily.chong@informa.com. 12.30 Lunch and poster / exhibition viewing time Basic Science and Current Disease Trends 14.00 KEYNOTE

Variant Creutzfeldt-Jakob disease and its transmission by blood vCJD represents the first known example of transmission of a prion agent from a non-human species to man. Since its identification, the number of vCJD cases in the UK has continued to increase, with additional cases identified over the past 10 years in France, Ireland, Canada, USA, Saudi Arabia, Japan, Netherlands, Italy, Spain and Portugal. 3 cases of probable vCJD transmission have occurred via blood transfusion and a recent risk assessment indicated that some plasma products produced in the UK might contain vCJD infectivity. Many uncertainties in this area could be addressed if a sensitive and specific screening test for vCJD was available. However, there will be major ethical dilemmas concerning the implementation of vCJD screening, since at present there is no effective treatment or prophylaxis for this devastating disorder.Professor James Ironside, Director of Laboratories,National CJD Surveillance Unit, University of Edinburgh, UK 14.30 Interaction of prions with other pathogenic insults During the years or decades of prion disease incubation, the at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections or inflammatory processes. Whether prion disease incubation time or otherwise the pathology of other diseases is affected by the co-infection process is unknown. In this work, we will show the effect of viral infection or induction of EAE on prion disease pathology.Dr D. Ruth Gabizon, Department of Neurology, Hadassah University Hospital, Israel 15.00 Prion in muscle from scrapie and BSE contaminated small ruminants In a first study susceptible genotype sheep were experimentally contaminated by oral or intracranial route (IC) using scrapie. In those animals, as well as in naturally scrapie-affected sheep (same scrapie isolate), PrPsc was detected not only in nerves – including intramuscular fibres – but also in a particular myocyte subset. In a second study PrPsc presence in muscle was investigated in goats. In natural scrapie affected goats from 3 different flocks, consistent PrPsc deposits were observed in various muscles. PrPsc was observed in muscle since 21 months old in apparently healthy animals.Dr Olivier Andreoletti, Animal Health Department, French National Veterinary School, France 15.30 Afternoon tea and poster / exhibition viewing time 16.00 Pathophysiology of human prion diseases: Distribution of PrPSc and beyond Human prion diseases are fatal neurodegenerative disorders. An essential part of the infectious agent, termed prion, is composed of an abnormal protein, PrP(Sc). In the course of the disease, PrP(Sc) deposits mainly in the central nervous system and to a lesser extent in non-neuronal tissues. Patterns of PrP(Sc) depositions both in the central nervous system and in peripheral organs may influence clinical symptoms and depend on various factors including host genotype.Professor Markus Glatzel, Director, Institute of Neuropathology,University Hamburg, Germany 16.30 TSE - Appreciation of surveillance and measures The sourcing of ruminant material with negligible risk for TSE is crucial for any use in the pharmaceutical industry. Specified risk materials have been identified for cattle and small ruminants. However, importance also must be given to the national TSE situation of a given country. The risk assessment should include an appreciation of the risk factors, the regulatory measures and the surveillance system in place. The results on the full implementation of the measures have to be assessed.Dr Lukas Perler, Head Technical Advice, Swiss Federal Veterinary Office, Switzerland 17.00 Cell culture models of prions to study transmission and to detect prions Cell culture models susceptible to prions represent relevant and useful experimental models. They allow the study of TSE molecular events, they can be used to detect the presence of infectivity and to validate therapeutic approaches. However, to date, only a few models are available and there is a real need in models able to propagate human prions and the BSE agent.Professor Sylvain Lehmann, Institute of Human Genetics, French National Center for Scientific Research (CNRS), France 17.30 End of day one followed by a drinks reception

08.30 Morning Coffee 09.00 Chairperson's Opening Remarks Advances in TSE Detection 09.05 Immunoassay for the detection of resistant prion protein (PrPres) in human plasma using an original combination of chemical ligands Streptomycin was found to aggregate PrPres in BSE or CJD brain samples after PK digestion. Another molecule, Calix-6-Arene sulfonate, was found to bind efficiently to PrPres aggregated by streptomycine, due to its "molecular basket" structure. A microplate immunoassay prototype for the detection of PrPres in human blood has been designed using the combined properties of these two molecules, with final specific antigenic detection using an anti-PrP monoclonal(s). Detection in blood of asymptomatic carriers and a test for excluding blood donations from such apparently healthy donors are next objectives. Further studies and technical improvements are therefore required before it may become a routine test for blood banking and/or human CJD diagnosis.Dr Hervé Perron, Research Director, R&D Immunoassay and Proteomics Department, BioMérieux, France 09.35 Safety measures protecting humans againts prion contamination: reduction of risk evaluated for oral exposure and for instrument contaminationDr Jean-Philippe Deslys, Coordinator of the European Network of Excellence NeuroPrion and Head of the Prion Research Group, French Atomic Energy Commission, France 10.05 Detection of prion proteins in body fluids Our group specialises in developing innovative technologies to detect prion proteins in animals and humans. We will present new data on the distribution of prion proteins in body fluids and on the detection of molecular markers after prion infection. These findings will be discussed in regard to prion transmission.Dr Ralph Zahn, Chief Executive Officer, Alicon AG, Switzerland 10.35 Morning coffee and poster / exhibition viewing time 11.00 Diagnostic assays for the detection of prions in blood The detection of PrPSc in blood of TSE infected animals and humans have been hampered by the low levels and lack of protease resistance of PrPSc in blood. We have developed proprietary technologies based on the ELISA and FACS platform for the detection of disease associated prion proteins in plasma and serum using the conformation specific antibody 15B3 which recognises protease sensitive forms of PrP.Dr Alex J. Raeber, Director of Research, Prionics AG, Switzerland 11.30 The use of Seprion for TSE blood screening The novel Seprion ligand system has been used for separating abnormal amyloid from the normal protein counterpart. The ligand has been incorporated into a EU and UDSA approved TSE assay which has 100% sensitivity and specificity. The potential of the ligand as a tool for CJD blood screening will be presented with an update on our scrapie time course studies.Dr Stuart Wilson, Scientific Director, Microsens Biotechnologies, UK 12.00 Technology TutorialTechnology providers will host interactive educational tutorials which address the benefits of their technology in the filed of TSE’s. If you would like to host a tutorial, please contact: lily.chong@informa.com. 12.30 Lunch and poster / exhibition viewing time 14.00 Application of the scrapie cell assay (SCA) to discriminate between different mouse prion strains and to determine the kinetics of in vitro generation of prions The scrapie cell assay is a rapid, cell-based method for the quantification of certain mouse prion strains. The assay can be readily performed in octuplicate on 80 samples in parallel and completed in two weeks, with a standard error of around 20%. Using the SCA we have determined that in vitro incubation of a small amount of scrapieinfected brain homogenate with PrPC (provided by normal mouse brain homogenate) under the conditions described by Lucassen et al. (Biochemistry, 42: 4127-35; 2003), generates a >10 fold increase of infectivity within 8 hrs.Dr Sukhvir P. Mahal, Department of Infectology, Scripps Florida, USA 14.30 Quantification of PrPres Extensive efforts are undertaken to develop tests for the detection of PrPres in live animals or for the screening of human blood. Several assays are basing upon immunochemical principles. By means of a sandwich ELISA with two monoclonal antibodies we’ve tested possibilities to quantify PrPres in different biological samples. This application allows the semi-quantitative screening of PrPres in these samples.Dr Ingolf Lachmann, Business Unit Manager Protein Diagnostics, AJ Roboscreen GmbH, Germany Industry Best Practices 15.00 TSE-safety of human urine-derived pharmaceuticals Human-derived pharmaceuticals originating from urine are now receiving a similar amount of regulatory attention as blood products. The need and the measures taken by Ferring Pharmaceuticals and other companies to ensure the safety of products such as urinary-derived gonadotrophins and urokinase will be described.Dr Peter A McAnulty, Senior Director, Non-Clinical Development, Ferring Pharmaceuticals A/S, Denmark 15.30 Afternoon tea and poster / exhibition viewing time Regulatory Perspectives 16.00 KEYNOTE

US approaches to prevent contamination of FDA-regulated products with the agents of Transmissible Spongiform Encephalopathies (TSEs) The US Food and Drug Administration (FDA) regulates vaccines, human blood and tissue products, drugs, surgical devices, cosmetics, many foods, animal feeds and veterinary drugs. FDA, uses regulations and guidance to help prevent contamination of regulated products with agents causing various TSEs: bovine spongiform encephalopathy, Creutzfeldt-Jakob Disease (CJD) and variant CJD.Dr David M. Asher, Chief, Laboratory of Bacterial, Parasitic and Unconventional Agents, Division of Emerging and Transfusion- Transmitted Diseases, Office of Blood Research and Review, CBER FDA, USA 16.30 TSE regulatory aspects in the EU In order to minimise the risk of transmission of BSE or other animal transmissible spongiform encephalopathy (TSE) agents via medicinal products, a guideline (“Note for Guidance on Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products”)is available to the pharmaceutical industry. A couple of revisions of this guideline have taken place and a new one is under preparation. The topics under revision will be detailed in presentation.Dr Sol Ruiz, Division of Biologicals and Biotechnology, Spanish Medicines Agency, Spain

Rapporteur for the TSE guideline at the European Medicines Agency and also for the TSE certification system at the European Pharmacopoeia 17.00 Reference reagents for pre-mortem vCJD diagnostic tests Homogenates from vCJD tissues have been spiked into cryo-depleted plasma at a range of concentrations within and beyond the current known levels of detection. To extend the range of samples available we have collaborated with the Veterinary Laboratories Agency (Weybridge, UK) to collect blood from scrapie infected and uninfected sheep. This blood has been fractionated into plasma, buffy coats and red blood cells. Preliminary studies using some of the samples described above have indicated their value in evaluating assay sensitivity and within and between laboratory variability.Dr Jillian Cooper, CJD Department, National Institute for Biological Standards and Control, (NIBSC), UK 17.30 End of Conference

16.30 TSE - Appreciation of surveillance and measures The sourcing of ruminant material with negligible risk for TSE is crucial for any use in the pharmaceutical industry. Specified risk materials have been identified for cattle and small ruminants. However, importance also must be given to the national TSE situation of a given country. The risk assessment should include an appreciation of the risk factors, the regulatory measures and the surveillance system in place. The results on the full implementation of the measures have to be assessed.Dr Lukas Perler, Head Technical Advice, Swiss Federal Veterinary Office, Switzerland

I was lucky enough to sit in on this BSE conference call today and even managed to ask a question. that is when the trouble started.

I submitted a version of my notes to Sandra Blakeslee of the New York Times, whom seemed very upset, and rightly so.

"They tell me it is a closed meeting and they will release whatever information they deem fit. Rather infuriating."

and i would have been doing just fine, until i asked my question. i was surprised my time to ask a question so quick.

(understand, these are taken from my notes for now. the spelling of names and such could be off.)

[host Richard Barns] and now a question from Terry S. Singeltary of CJD Watch.

[TSS] yes, thank you, U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[no answer, you could hear in the back ground, mumbling and 'we can't. have him ask the question again.]

[host Richard] could you repeat the question?

[TSS] U.S. cattle, what kind of guarantee can you give for serum or tissue donor herds?

[not sure whom ask this] what group are you with?

[TSS] CJD Watch, my Mom died from hvCJD and we are tracking CJD world-wide.

[not sure who is speaking] could you please disconnect Mr. Singeltary

[TSS] you are not going to answer my question?

[not sure whom speaking] NO

from this point, i was still connected, got to listen and tape the whole conference. at one point someone came on, a woman, and ask again;

[unknown woman] what group are you with?

[TSS] CJD Watch and my Mom died from hvCJD we are trying to tract down CJD and other human TSE's world wide. i was invited to sit in on this from someone inside the USDA/APHIS and that is why i am here. do you intend on banning me from this conference now?

at this point the conference was turned back up, and i got to finish listening. They never answered or even addressed my one question, or even addressed the issue. BUT, i will try and give you a run-down for now, of the conference.

IF i were another Country, I would take heed to my notes, BUT PLEASE do not depend on them. ask for transcript from;

RBARNS@ORA.FDA.GOV 301-827-6906

he would be glad to give you one ;-)

Rockville Maryland, Richard Barns Host

BSE issues in the U.S., How they were labelling ruminant feed? Revising issues.

The conference opened up with the explaining of the U.K. BSE epidemic winding down with about 30 cases a week.

although new cases in other countries were now appearing.

Look at Germany whom said NO BSE and now have BSE.

BSE increasing across Europe.

Because of Temporary Ban on certain rendered product, heightened interest in U.S.

A recent statement in Washington Post, said the New Administration (old GW) has a list of issues. BSE is one of the issues.

BSE Risk is still low, minimal in U.S. with a greater interest in MBM not to enter U.S.

HOWEVER, if BSE were to enter the U.S. it would be economically disastrous to the render, feed, cattle, industries, and for human health.

(human health-they just threw that in cause i was listening. I will now jot down some figures in which they told you, 'no need to write them down'. just hope i have them correct. hmmm, maybe i hope i don't ???)

80% inspection of rendering

*Problem-Complete coverage of rendering HAS NOT occurred.

sizeable number of 1st time FAILED INITIAL INSPECTION, have not been reinspected (70% to 80%).

Compliance critical, Compliance poor in U.K. and other European Firms.

NON-FDA licensed mills There is NO inventory on non licensed mills. approximately 6000 to 8000 Firms ??? 4,344 ever inspected. "FDA does not have a lot of experience with"

40% do NOT have caution statement 'DO NOT FEED'.

74% Commingling compliance

"This industry needs a lot of work and only half gotten to"

"700 Firms that were falitive, and need to be re-inspected, in addition to the 8,000 Firms."

Quote to do BSE inspection in 19 states by end of January or 30 days, and other states 60 days. to change feed status??? Contract check and ask questions and pass info.

At this time, we will take questions.

[I was about the third or fourth to ask question. then all B.S.eee broke loose, and i lost my train of thought for a few minutes. picked back up here]

someone asking about nutritional supplements and sourcing, did not get name. something about inspectors not knowing of BSE risk??? the conference person assuring that Steve Follum? and the TSE advisory Committee were handling that.

Some other Dr. Vet, whom were asking questions that did not know what to do???

USDA/APHIS would like to provide clarification on the following point from Mr. Singeltary's 9 Jan posting regarding the 50 state conference call.

[Linda Detwiler asking everyone (me) not to use emergency BSE number, unless last resort. (i thought of calling them today, and reporting the whole damn U.S. cattle herd ;-) 'not']

Dr. Detwiler was responding to an announcement made during the call to use the FDA emergency number if anyone wanted to report a cow with signs suspect for BSE. Mr. Singeltary is correct that Dr. Detwiler asked participants to use the FDA emergency number as a last resort to report cattle suspect for BSE. What Mr. Singeltary failed to do was provide the List with Dr. Detwiler's entire statement. Surveillance for BSE in the United States is a cooperative effort between states, producers, private veterinarians, veterinary hospitals and the USDA. The system has been in place for over 10 years. Each state has a system in place wherein cases are reported to either the State Veterinarian, the federal Veterinarian in Charge or through the veterinary diagnostic laboratory system. The states also have provisions with emergency numbers. Dr. Detwiler asked participants to use the systems currently in place to avoid the possibility of a BSE-suspect report falling through the cracks. Use of the FDA emergency number has not been established as a means to report diseased cattle of any nature.

> What Mr. Singeltary failed to do was provide > the List with Dr. Detwiler's entire statement.

would you and the USDA/APHIS be so kind as to supply this list with a full text version of the conference call and or post on your web-site? if so when, and thank you. if not, why not?

> The system has been in place for over 10 years.

that seems to be a very long time for a system to be in place, and only test 10,700 cattle from some 1.5 BILLION head (including calf crop). Especially since French are testing some 20,000 weekly and the E.U. as a whole, are testing many many more than the U.S., with less cattle, same risk of BSE/TSEs.

Why does the U.S. insist on not doing massive testing with the tests which the E.U. are using? Why is this, please explain?

Please tell me why my question was not answered?

> U.S. cattle, what kind of guarantee can you > give for serum or tissue donor herds?

It was a very simple question, a very important question, one that pertained to the topic of BSE/feed, and asked in a very diplomatic way. why was it not answered?

If all these years, we have been hearing that pharmaceutical grade bovines were raised for pharmaceuticals vaccines etc. But yet the USA cannot comply with feed regulations of the ruminant feed ban, PLUS cannot even comply with the proper labelling of the feed, cross contamination etc. Then how in the world can you Guarantee the feed fed to pharmaceutical grade bovine, were actually non ruminant feed?

Before i was ask to be 'disconnected', i did hear someone in the background say 'we can't'-- have him ask the question again.

could you please be so kind, as to answer these questions?

thank you, Terry S. Singeltary Sr. Bacliff, Texas USA

P.S. if you will also notice, i did not post that emergency phone number and do not intend on passing it on to anyone. I was joking when i said i should call and report the whole damn U.S. Herd. So please pass that on to Dr. Detwiler, so she can rest easily.

BUT, they should be reported, some are infected with TSE. The U.S. is just acting as stupid as Germany and other Countries that insist they are free of BSE.

Because of this report, and the recent findings of the 50-state BSE Conference call, I respectfully seriously suggest that these Countries and the SSC re-evaluate the U.S.A. G.B.R. to a risk factor of #3.

I attempted to post this to list in full text, but would not accept...

thank you, kind regards, Terry S. Singeltary Sr., Bacliff, Texas USA

Report on the assessment of the Geographical BSE-risk of the USA July 2000

PART II

REPORT ON THE ASSESSMENT OF THE GEOGRAPHICAL BSE RISK OF THE UNITED STATES OF AMERICA

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Report on the assessment of the Geographical BSE-risk of the USA July 2000

EXECUTIVE SUMMARY

OVERALL ASSESSMENT

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

Stability: Before 1990 the system was extremely unstable because feeding of MBM to cattle happened, rendering was inappropriate with regard to deactivation of the BSE-agent and SRM and fallen stock were rendered for feed. From 1990 to 1997 it improved to very unstable, thanks to efforts undertaken to trace imported animals and exclude them from the feed chain and intensive surveillance. In 1998 the system became neutrally stable after the RMBM-ban of 1997.

External challenges: A moderate external challenge occurred in the period before 1990 because of importation of live animals from BSE-affected countries, in particular from the UK and Ireland. It cannot be excluded that some BSE-infected animals have been imported by this route and did enter the US rendering and feed production system. The efforts undertaken since 1990 to trace back UK-imported cattle and to exclude them from the feed chain reduced the impact of the external challenge significantly.

Interaction of external challenges and stability: While extremely unstable, the US system was exposed to a moderate external challenge, mainly resulting from cattle imports from the UK. It can not be excluded that BSE-infectivity entered the country by this route and has been recycled to domestic cattle. The resulting domestic cases would have been processed while the system was still very unstable or unstable and would hence have initiated a number of second or third generation cases. However, the level of the possible domestic prevalence must be below the low detection level of the surveillance in place.

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent will remain at the current level.

JUSTIFICATION

1. DATA

The available information was suitable to carry out the GBR risk assessment.

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Report on the assessment of the Geographical BSE-risk of the USA July 2000

2. STABILITY

2.1 Overall appreciation of the ability to identify BSE-cases and to eliminate animals at risk of being infected before they are processed

· Before 1989, the ability of the system to identify (and eliminate) BSE cases was limited. · Since 1990 this ability is significantly improved, thanks to a good BSE-surveillance and culling system (contingency plan). · Today the surveillance should be able to detect clinical BSE-cases within the limits set by an essential passive surveillance system, i.e. some cases might remain undetected.

2.2 Overall appreciation of the ability to avoid recycling BSE-infectivity, should it enter processing

· Before 1997 the US rendering and feed producing system would not have been able to avoid recycling of the BSE agent to any measurable extent. If the BSE-agent was introduced the feed chain, it could probably have reached cattle. · After the introduction of the RMBM-to-ruminants-ban in August 1997 the ability of the system to avoid recycling of BSE-infectivity was somewhat increased. It is still rather low due to the rendering system of ruminant material (including SRM and fallen stock) and the persisting potential for cross-contamination of cattle feed with other feeds and hence RMBM.

2.3 Overall assessment of the Stability

· Until 1990 the US BSE/cattle system was extremely unstable as RMBM was commonly fed to cattle, the rendering system was not able to reduce BSE-infectivity and SRM were rendered. This means that incoming BSE infectivity would have been most probably recycled to cattle and amplified and the disease propagated. · Between 1990 and 1995 improvements in the BSE surveillance and the efforts to trace back and remove imported cattle gradually improved the stability but the system remained very unstable. In 1998 the system became unstable because of an RMBM-ban introduced in 1997. After 1998 the ban was fully implemented and the system is regarded to be neutrally stable since 1998. The US system is therefore seen to neither be able to amplify nor to reduce circulating or incoming BSE-infectivity.

3. CHALLENGES

A moderate external challenge occurred in the period 1980-1989 because of importation of live animals from the UK. imports from other countries are regarded to have been negligible challenges. · As a consequence of this external challenge, infectivity could have entered the feed cycle and domestic animals could have been exposed to the agent. These domestic BSE-incubating animals might have again entered processing, leading to an internal challenge since 1991. · This internal challenge could have produced domestic cases of BSE, yet prevalence levels could have been below the detection limits of the surveillance system until now. (According to US calculations, the current surveillance

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Report on the assessment of the Geographical BSE-risk of the USA July 2000

system could detect clinical incidence of 1-3 cases per year per million adult cattle, i.e. in absolute numbers 43-129 cases per year). Between 1990 und 1995, with the exclusion of the imported animals from Europe from the feed chain, the effect of the external challenges decreased.

4. CONCLUSION ON THE RESULTING RISKS

4.1 Interaction of stability and challenqe

· In the late 80s, early 90s a moderate external challenges met an extremely unstable system. This would have amplified the incoming BSE-infectivity and propagated the disease. · With the exclusion of the imported animals from Europe from the feed chain between 1990 and 1995 the effect of the external challenge decreased. · Before 1998 an internal challenge, if it developed, would have met a still unstable system (inappropriate rendering, no SRM ban, RMBM ban only after 1997) and the BSE-infectivity could have been recycled and amplified. · After 1998 the neutrally stable system could still recycle the BSE-agent but due to the RMBM-ban of 1997 the BSE-infectivity circulating in the system would probably not be amplified.

4.2 Risk that BSE-infectivity enters processing

· A very low processing risk developed in the late 80s when the UK-imports were slaughtered or died. It increased until 1990 because of the higher risk to be infected with BSE of cattle imported from the UK in 1988/89, as these animals could have been processed prior to the back-tracing of the UK-imports in 1990. · From 1990 to 1995 a combination of surviving non-traced UK imports and some domestic (pre-)clinical cases could have arrived at processing resulting in an assumed constant low but non-negligible processing risk. · After 1995 any processing risk relates to assumed domestic cases arriving at processing. · The fact that no domestic cases have been shown-up in the BSE-surveillance is reassuring - it indicates that BSE is in fact not present in the country at levels above the detection limits of the country's surveillance system. This detection level has been calculated according to US-experts to be between 1 & 3 clinical cases per million adult cattle per year.

Note: The high turnover in parts of the dairy cattle population with a young age at slaughter makes it unlikely that fully developed clinical cases would occur (and could be detected) or enter processing. However, the theoretical infective load of the pre-clinical BSE-cases that under this scenario could be processed, can be assumed to remain relatively low.

4.3 Risk that BSE-infectivity is recycled and propagated

· During the period covered by this assessment (1980-1999) the US-system was not able to prevent propagation of BSE should it have entered, even if this ability was significantly improved with the MBM-ban of 1997. · However, since the likelihood that BSE-infectivity entered the system is regarded to be small but non-negligible, the risk that propagation of the disease took place is also small but not negligible.

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Report on the assessment of the Geographical BSE-risk of the USA July 2000

5. CONCLUSION ON THE GEOGRAPHICAL BSE-RISK

5.1 The current GBR

The current geographical BSE-risk (GBR) level is II, i.e. it is unlikely but cannot be excluded that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent.

5.2 The expected development of the GBR

As long as there are no changes in stability or challenge the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent remains at the current level.

5.3 Recommendations for influencin.q the future GBR

· As long as the stability of the US system is not significantly enbanced above neutral levels it remains critically important to avoid any new external challenges. · All measures that would improve the stability of the system, in particular with regard to its ability to avoid recycling of the BSE-agent should it be present in the cattle population, would reduce, over time, the probability that cattle could be infected with the BSE-agent. Possible actions include: removal of SRMs and/or fallen stock from rendering, better rendering processes, improved compliance with the MBM-ban including control and reduction of cross-contamination. · Results from an improved intensive surveillance programme, targeting at risk sub-populations such as adult cattle in fallen stock or in emergency slaughter, could verify the current assessment.

PLUS, if the USA continues to flagrantly ignore the _documented_ science to date about the known TSEs in the USA (let alone the undocumented TSEs in cattle), it is my opinion, every other Country that is dealing with BSE/TSE should boycott the USA and demand that the SSC reclassify the USA BSE GBR II risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_ any longer on this issue, should also be regarded with great suspicion as well. NOT to leave out the OIE and it's terribly flawed system of disease surveillance. the OIE should make a move on CWD in the USA, and make a risk assessment on this as a threat to human health. the OIE should also change the mathematical formula for testing of disease. this (in my opinion and others) is terribly flawed as well. to think that a sample survey of 400 or so cattle in a population of 100 million, to think this will find anything, especially after seeing how many TSE tests it took Italy and other Countries to find 1 case of BSE (1 million rapid TSE test in less than 2 years, to find 102 BSE cases), should be proof enough to make drastic changes of this system. the OIE criteria for BSE Country classification and it's interpretation is very problematic. a text that is suppose to give guidelines, but is not understandable, cannot be considered satisfactory. the OIE told me 2 years ago that they were concerned with CWD, but said any changes might take years. well, two years have come and gone, and no change in relations with CWD as a human health risk. if we wait for politics and science to finally make this connection, we very well may die before any decisions or changes are made. this is not acceptable. we must take the politics and the industry out of any final decisions of the Scientific community. this has been the problem from day one with this environmental man made death sentence. some of you may think i am exaggerating, but you only have to see it once, you only have to watch a loved one die from this one time, and you will never forget, OR forgive...yes, i am still very angry... but the transmission studies DO NOT lie, only the politicians and the industry do... and they are still lying to this day...TSS

EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR) of the United States of America (USA) Last updated: 19 July 2005 Adopted July 2004 (Question N° EFSA-Q-2003-083)

Report Summary Summary of the Scientific Report

The European Food Safety Authority and its Scientific Expert Working Group on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE) Risk (GBR) were asked by the European Commission (EC) to provide an up-to-date scientific report on the GBR in the United States of America, i.e. the likelihood of the presence of one or more cattle being infected with BSE, pre-clinically as well as clinically, in USA. This scientific report addresses the GBR of USA as assessed in 2004 based on data covering the period 1980-2003.

The BSE agent was probably imported into USA and could have reached domestic cattle in the middle of the eighties. These cattle imported in the mid eighties could have been rendered in the late eighties and therefore led to an internal challenge in the early nineties. It is possible that imported meat and bone meal (MBM) into the USA reached domestic cattle and leads to an internal challenge in the early nineties.

A processing risk developed in the late 80s/early 90s when cattle imports from BSE risk countries were slaughtered or died and were processed (partly) into feed, together with some imports of MBM. This risk continued to exist, and grew significantly in the mid 90’s when domestic cattle, infected by imported MBM, reached processing. Given the low stability of the system, the risk increased over the years with continued imports of cattle and MBM from BSE risk countries.

EFSA concludes that the current GBR level of USA is III, i.e. it is likely but not confirmed that domestic cattle are (clinically or pre-clinically) infected with the BSE-agent. As long as there are no significant changes in rendering or feeding, the stability remains extremely/very unstable. Thus, the probability of cattle to be (pre-clinically or clinically) infected with the BSE-agent persistently increases.